Higher free thyroxine levels predict increased incidence of dementia in older men. The Health In Men Study. (#60)
Both hypothyroidism and subclinical hyperthyroidism hinder cognitive function. However, it is unclear whether differences in thyroid hormone levels within the normal range might modulate risk of dementia particularly in older adults.
We aimed to determine whether more subtle alterations of thyroid hormone levels predict increased incidence of dementia in ageing men.
Prospective longitudinal study.
Community-dwelling men aged 70-89 years.
Main outcome measures
The Standardised Mini-mental State Examination (SMMSE) was performed at baseline (2001-2004), and circulating thyrotropin (TSH) and free thyroxine (FT4) were assayed. Men with known thyroid disease or dementia, or SMMSE<24 were excluded from follow-up. New-onset dementia, defined by ICD codes, was ascertained using data linkage (2001-2009).
During follow-up 147 of 3,408 men (4.3%) were diagnosed for the first time with dementia. Men who developed dementia had higher baseline FT4 (16.6±2.5 vs 16.0±2.3 pmol/L, p<0.001), but similar TSH (2.2±1.4 vs 2.3±1.6 mU/L, p=0.22) compared with men who did not receive this diagnosis. After adjusting for age, body mass index, smoking, education, baseline SMMSE, medical comorbidities, social support and sensorial impairment, higher FT4 predicted new-onset dementia (quartiles, Q2-Q4 vs Q1: adjusted HR=1.79, 95%CI=1.05-3.05). There was no association between TSH quartiles and incident dementia. When the analysis was restricted to euthyroid men (excluding those with subclinical hyper- or hypo-thyroidism), higher FT4 remained associated with incident dementia (two-fold increase in adjusted HR for Q2-Q4, p=0.001 for trend).
Higher FT4 levels predict new-onset dementia in older men, independently of conventional risk factors for cognitive decline. This association is robust to adjustment for covariates and remains significant in euthyroid men. Further studies are needed to explore potential underlying mechanisms, and to clarify the utility of thyroid function testing in older men at risk of dementia.